Cell and DNA and blood

1. G1
2. G2
3. M

1. Cyclin dependent kinases CDK
   1. Phosphorylate things
2. Cyclins

1. Longest part
2. Controls length of cell cycle
3. Duplicates cell organells
4. Starts replicating centresomes

1. Prophase
   1. chromosomes start condensing
      1. chromosomes
         1. acrocentric
            1. no p arm
         2. metcentric
            1. centromere in the middle
               1. 1,3
         3. submetacentric
            1. 2-12,16-19, 23
2. Metaphase
3. anaphase
4. Telophase

1. Terms
   1. Pyknosis

      Anmerkungen:

      • Nucleus shrinkage
   2. Karyolysis

      Anmerkungen:

      • Nucleus fading
   3. Karyorrhexis

      Anmerkungen:

      • Nucleus fragmenting
2. Mechanism

   Anmerkungen:

   • https://www.youtube.com/watch?v=wREkXDiTkPs 
   1. Extrinsic
      1. Activate receptors

         Anmerkungen:

         • (Fas death receptors and lethal ligands)
         1. Activates Procaspase 8
            1. Caspase 8
               1. Procaspase 3
   2. Intrinsic
      1. Cellular stress within the mitochondria
         1. Releases Cytochrome C
            1. Activates Procaspase 9

               Anmerkungen:

               • sticks to a apoptosome (looks like a flower)
               1. Activates Caspase 9
                  1. Activates Caspase 3

                     Anmerkungen:

                     • Executioner procaspases Actiavtes DNAse- DNA broken down.  Also cleaves cytoskeleton
                     1. Caspase cascade
                        1. Apoptosis
         2. And Bid (protein)

            Anmerkungen:

            • Activates caspase 8
   3. CD8/ NK cells

1. Leads to influx or ions and water so cells swell and bursts
2. In DNA extraction, lots of DNA no order of size
3. Can get centre of tumour necrosis as not enough blood supply
4. Types
   1. Coagulative
      1. Hypoxic/ischaemic but not the brain
      2. Architecture preserved
   2. Liquefactive
      1. Loss of architecture
      2. Abscess formed
         1. Eventually walled off by fibrous capsule
      3. Infection or brain infarct
   3. Caseous
      1. TB
      2. Inflammatory cells
      3. Cheesy
   4. Fibrinoid
      1. Eosinophilic
      2. Bright pink appearance
   5. Fat
      1. irregular cell outlines
      2. Pink mass

1. Molecule binds to cell

Anmerkungen:

• In nucleus. Nuclear membrane is formed, makes extra for ER and patching up cell membrane

1. Gene transcription factor binds to DNA
   1. RNA polymerase binds next to it
      1. Activator activates RNA polymeras
         1. Regulatory region
         2. Can bind far away so DNA folds on itself, mediator inbetween activator and RNA polymerase
   2. promoter (enhancer) region
   3. Repressors can also bind here- blocking
      1. also work by
         1. disturbing signals between activator and RNA polymerase
         2. Making chromatin coil up tightly so nothing can bind
2. Epigenetics
   1. Methylation
      1. hypermethylation= off
   2. Histone modification

1. Introns- non coding
2. Exons- coding
3. 5' cap
4. Poly- A- tail
5. 5- UTR region
6. 3- UTR regions
7. micro- RNAs break down mRNAs

1. Ribosomal Subunits
   1. 60s- big one on top
      1. EPA
         1. E exit
   2. 40 s
2. tRNA
   1. 3 loops
      1. T loop
      2. Anticodon loop
      3. D loop
3. Initiation
   1. MET phosphorylated
      1. Joins to tRNA
         1. elf brings tRNA and 40s subunit, starts in P section
   2. ATP brings large subunit 60s
   3. Elongation
      1. eFF brings next tRNA
      2. Termination
         1. eRF
            1. release factor complex
      3. peptidyl transferase- forms peptide bond between the amino acids

1. ER associated degradation pathway ERAD
   1. If protein goes wrong
2. Unfolded protein response UPR
   1. more chaperones to help with proteins
      1. Chaperones fold proteins
3. ER stress
   1. lots of protein not folded properly
4. when things go wrong
   1. prion disease
      1. lots of misfolded prions
         1. prion- something that can fold in multiple ways
      2. symptoms similar to huntingtons- communication, movement, memory

1. On outside is SNARE proteins which control where it goes

1. Dimerisation
   1. 2 identical proteins form complex

1. N-acytl-galactosamine

1. Galactose

1. IgM against ABO blood markers
2. IgG against Rh+
   1. IgG is passed through placenta

1. D antigen
   1. haemolytic disease
      1. Prevent by anti-D immunoglobulin treatment
2. dominant gene

1. multilayered

1. single-layered

1. Keratinised
   1. loss of nucleus in top layer
2. Non-keratinised
   1. Have nuclei in top layer

1. Apical domain
   1. Cillia
   2. Microvilli

1. in between cells
   1. Junctions
      1. Tight junciton
         1. Zona occludens
         2. In stratum granulosum
      2. Desmosomes
         1. Connect adjacent cells on surface
            1. Macular adherens
      3. Anchoring junction
         1. Connect cytoskeletons of adjacent cells
            1. Zona adherens
      4. Gap junction
         1. Cell-cell communication

1. Basement membrane infoldings
   1. increase SA
2. Cell-extracellular matrix junctions
3. Hemidesmosome
   1. Between cell and basement membrane

1. autosomal
   1. dominant
   2. recessive
      1. more common in consanguineous relationships
         1. consanguineous = related by blood
2. X linked
   1. dominant
      1. males more severely affected
   2. recessive

1. exists in more than one form
2. Variation in genetics with is used to describe variation which is present in >1% of population
3. SNP= single nucleotide polymorphisms
   1. Only 2 forms

1. change in DNA in=<1% of population

1. Repeated sequences 2-4 bp long
2. Microsatellites
   1. STR
      1. Short Tandem Repeats
3. Can use in paternity testing, and genetic fingerprinting

1. radiation
2. oxidative stress
   1. metabolic damage
3. replication error

1. Very long sequences (1000bp) which can vary in the number of copies you can have

1. translocation
2. deletion
3. Insertation

   Anmerkungen:

   • Usually results in stop codon Can cause frame shift

1. heritable change in genetic material
2. Name
   1. p.Phe508del
      1. p= protein affected
      2. Phe= normal amino acid
      3. 508= location
      4. del= deletion

         Anmerkungen:

         • Name of another amino acid here if substitution 
3. Philadelphian mutation- translocation of chromosome 9 and 22

   Anmerkungen:

   • associated with leukaemia 
4. Terms
   1. Haploinsufficiency

      Anmerkungen:

      • Usually have 2 alleles. If one is mutated and doesn't work, one functioning allele left. It can't produce enough protein by itself= loss of function
   2. dominant negative

      Anmerkungen:

      • One mutated protein affects the others
   3. Gain of function

      Anmerkungen:

      • Activated oncogenes leading to neoplasms

1. Single base change
   1. Substitution
      1. Splicing mutation
      2. Change in nucleic acid
         1. Missense
            1. Different amino acid
            2. most common cause of CF
         2. Nonsense
            1. STOP codon

1. Difference in a persons nucleotide
   1. i.e. a different base
2. usually between genes
3. SNP genotyping
   1. Chip has different SNPs on it
      1. Patient DNA with florescent probe added
         1. Will stick by hybridisation if present
            1. Will show up as florescent if have that SNP
4. Blocks of genome is inherited
   1. So if have certain SNP more likely to have certain disease

1. Single gene

1. Microarray
   1. provides genotype analysis for the variants on the chip
   2. Has all short parts of DNA from a particular gene attached
      1. including possible variants that the person might have
2. Whole genome sequencing WGS
3. Genome wide association
   1. tell you how likely it is you could get a certain disease from your genes

1. confirm clinical diagnosis
2. Provide accurate prognosis

1. Test for late-onset disease

1. Parents might use this before they choose to have a baby

1. preimplantation genetic diagnosis
   1. PGD- used in IVF
2. CVS/ amniocentesis

1. consumerism genetic test

1. Physical examination
   1. phenotype
2. Biochemical tests
   1. phenotype
3. DNA analysis
   1. genotype